Toxicon最新文献

{"title":"Road Guarder (Conophis lineatus concolor: Dipsadidae): Case documentation of a clinically significant envenoming","authors":"D.E. Keyler","doi":"10.1016/j.toxicon.2024.108215","DOIUrl":"10.1016/j.toxicon.2024.108215","url":null,"abstract":"<div><div>Detailed cases of envenoming by a non-front-fanged snake (NFFS) from North, Central, and South America have had limited representation in the toxicology and toxinology literature. The NFFS, <em>Conophis lineatus</em>, has been reported to deliver bites that resulted in moderately severe envenoming. However, most of these reported cases have been via personal communication, or self-reported and lacking in detailed medical evaluations. Reported here is a case of an amateur naturalist who was traveling in Mexico and was envenomed following extensive protracted bites to both hands from a wild <em>Conophis lineatus concolor</em>. There was rapid development of extensive localized edema, intense pain, and ecchymoses. The patient was transported to a hospital and after arrival the administration of antivenom was considered due to the severe appearance of local symptoms. The patient requested the medical team contact a consultant toxinologist who advised against the administration of antivenom because of the absence of any supporting evidence demonstrating therapeutic benefit in treating envenoming by <em>C. l. concolor</em>. Consequently, all treatments were limited to supportive symptomatic care. Despite the development of prominent localized symptoms, all laboratory evaluations, including coagulopathy assessment values, revealed no remarkable abnormal alterations. The patient was discharged after two days and symptoms gradually resolved with two months of supportive care.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108215"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"18beta-glycyrrhetinic acid alleviates deoxynivalenol-induced hepatotoxicity by inhibiting GPX4-dependent ferroptosis","authors":"Chenchen Song ,&nbsp;Wei Wang ,&nbsp;Yu Hua ,&nbsp;Aimei Liu","doi":"10.1016/j.toxicon.2025.108228","DOIUrl":"10.1016/j.toxicon.2025.108228","url":null,"abstract":"<div><div>Deoxynivalenol (DON), a mycotoxin that severely contaminates agri-food products can cause hepatotoxicity. Ferroptosis is an iron-dependent form of cell death, and the liver is an important organ for iron accumulation. 18beta-glycyrrhetinic acid (GA) has anti-ferroptosis and hepatoprotective effects. This study aimed to investigate the role of ferroptosis in the protective effects of GA against DON-induced hepatotoxicity in HepG2 cells and mice. The in vitro results revealed that DON (0.4 μM) decreased GPX4, SLC7A11, GCLC, NQO1, and Nrf2 expression; promoted TFR-1 expression and MDA, 4-HNE, and total ROS production; accelerated GSH depletion; and enhanced lipid ROS accumulation and Fe(II) overload, leading to ferroptosis. Pre-treatment with GA (0.4 and 6 μM) reversed these changes and alleviated DON-induced ferroptosis, thereby increasing cell viability and proliferation. In vivo results also showed that GA (10 mg/kg bw) pre-administration attenuated DON (2 mg/kg bw)-induced mouse liver injury, in part by inhibiting ferroptosis through reducing mitochondrial damage and lipid peroxidation. In addition, GA prevented erastin- and RSL3-induced ferroptosis by promoting GPX4 and SLC7A11 expression. Altogether, GA attenuated DON-induced hepatotoxicity by preventing ferroptosis via activation of GPX4-dependent pathway. The findings of this study provide a theoretical basis for the prevention of food mycotoxin toxicity.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108228"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on botulinum toxin treatment of painful diabetic neuropathy, post-traumatic painful neuropathy/neuralgia, post-herpetic neuralgia and occipital neuralgia","authors":"Bahman Jabbari ,&nbsp;Ava Tohidian","doi":"10.1016/j.toxicon.2025.108237","DOIUrl":"10.1016/j.toxicon.2025.108237","url":null,"abstract":"<div><div>The literature in botulinum toxin treatment for painful diabetic neuropathy (PDN), post traumatic neuralgia (PTN), postherpetic neuralgia (PHN) and occipital neuralgia (ON) was reviewed up to Oct 1st, 2024. Using the efficacy criteria set forth by the Assessment and Guideline subcommittee of the American Academy of Neurology, the current levels of efficacy for these conditions could be designated as followings: PDN: B (probably effective, two class II study), PTN: A (effective, two class I studies); PHN: A (effective, two class I studies), ON: (undetermined due to lack of blinded investigations). Due to the small number of patients in these studies, proof of efficacy requires conduction of controlled and blinded studies in large cohorts of patients with longer follow ups. Future prospects of botulinum therapy for these pain disorders were discussed along with the advantages of this mode of treatment over the current modes of treatment.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108237"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Sophora alkaloid poisoning in Hong Kong","authors":"Tsz Kit Chow ,&nbsp;Rex Pui Kin Lam ,&nbsp;Chi Keung Chan ,&nbsp;Man Li Tse ,&nbsp;Yibin Feng ,&nbsp;Timothy Hudson Rainer","doi":"10.1016/j.toxicon.2025.108251","DOIUrl":"10.1016/j.toxicon.2025.108251","url":null,"abstract":"<div><div><em>Sophora</em> alkaloids, including matrine, oxymatrine, and sophoridine, are quinolizidines found in plants used in traditional Chinese medicine such as <em>Sophora flavescens</em> and <em>Sophora tonkinensis</em>. Reports on acute <em>Sophora</em> alkaloid poisoning in humans outside of mainland China are lacking. This study aimed to characterize the clinical presentations, management, and outcomes of acute poisoning involving <em>Sophora</em> alkaloids in Hong Kong. We conducted a retrospective study of patients who were reported to the Hong Kong Poison Control Centre from all public emergency departments (EDs) in Hong Kong for acute poisoning involving <em>Sophora</em> alkaloids. Exposure was confirmed by laboratories, and data were collected between July 1, 2008 and June 30, 2021. We also analyzed patient demographics, clinical, management, and outcome characteristics. Among the 83 cases analyzed, <em>S. flavescens</em> was the major source (77.1%) of <em>Sophora</em> alkaloids and excessive dose was common (39.0%). Most patients (90.4%) had minor effects. Common clinical presentations were dizziness (83.1%), vomiting (72.3%), and palpitations (32.5%). No acute liver or kidney injuries or adverse skin reactions were observed. Treatment was primarily supportive and no patients underwent gastrointestinal decontamination, organ support treatment, or renal replacement therapy. Most patients (74.7%) were observed in the ED and only one required close monitoring in a cardiac care unit for prolonged QT interval after concurrent ciprofloxacin use. In contrast to the intravenous administration of <em>S. flavescens</em>, no adverse skin reactions were seen after oral consumption. Hepatoxicity, reported in <em>in vitro</em> and animal studies, and isolated human case reports, was not observed. In conclusion, excessive dose of <em>S. flavescens</em> is a common cause of acute <em>Sophora</em> alkaloid poisoning. Although most patients had mild symptoms, discrepancies in clinical presentations resulting from different formulations and varied experimental/clinical conditions call for further studies to evaluate the real-world risks of skin reactions and hepatoxicity of <em>Sophora</em> alkaloids.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108251"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necroptosis signaling in spatial memory impairment caused by Aflatoxin B1 in male mice; involvement of the nitric oxide pathway","authors":"Amin Haghighat Naeini ,&nbsp;Ehsan Nassireslami ,&nbsp;Marjan Shariatpanahi ,&nbsp;Mohsen Chamanara ,&nbsp;Ali Abdolali ,&nbsp;Mehdi Aghsami","doi":"10.1016/j.toxicon.2025.108272","DOIUrl":"10.1016/j.toxicon.2025.108272","url":null,"abstract":"<div><div>Aflatoxin B1 is the most toxic form of aflatoxins found in food. Nitric oxide in the hippocampus is essential for learning and memory. Necroptosis plays a role in cell death and pathology of many diseases, including neurodegenerative diseases. This study aimed to explore the role of the nitric oxide pathway and necroptosis signaling in Aflatoxin B1 neurotoxicity. A total of 35 male NMRI mice were divided into 5 groups as follows: Control group, Aflatoxin B1, Aflatoxin B1+L-Arginine, Aflatoxin B1+Aminoguanidine, and Aflatoxin B1+L-NAME. The spatial memory of the mice was assessed using the Barnes Maze test, and Western blot was conducted to evaluate the expression of RIP1, RIP3 and MLKL biomarkers in the hippocampus of mice brain. The behavioral tests indicated a significant memory impairment caused by Aflatoxin B1, which was significantly altered by L-Name and Aminoguanidine. The molecular tests showed an elevation of RIP1, RIP3 and MLKL biomarkers triggered by Aflatoxin B1 and a significant neutralization was then observed by L-Name. This study demonstrated that necroptosis pathway could be a possible mechanism of AFB1-induced memory damages and the nitric oxide pathway could play a role in altering these changes.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"256 ","pages":"Article 108272"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation in venom yield, protein concentration and regeneration toxicity in the scorpion Buthus lienhardi","authors":"Mehdi Ait Laaradia ,&nbsp;Jawad Laadraoui ,&nbsp;Amina Ettitaou ,&nbsp;Fatimzahra Agouram ,&nbsp;Khadija Oubella ,&nbsp;Soad Moubtakir ,&nbsp;Rachida Aboufatima ,&nbsp;Abderrahman Chait","doi":"10.1016/j.toxicon.2025.108254","DOIUrl":"10.1016/j.toxicon.2025.108254","url":null,"abstract":"<div><div>Scorpion venom research aims to develop treatments for dangerous species and identify candidates for new drugs. The extraction of high-quality venom, which is essential, requires mastery of the extraction and maintenance of scorpions. It is in this perspective that we have undertaken this present work which aims to contribute to scientifically mastering venom yields and the factors that influence them in scorpions.</div><div>Two experiments were conducted. In the first, the volume yield and protein concentration of venom from 121 <em>Buthus lienhardi</em> scorpions were examined according to their size, sex, mass and place of origin. In the second experiment, the quality and quantity of venom regenerated over 30 days after extraction were measured on 80 scorpions, with samples collected at different time points (8 H, 16 H, 24 H, 32 H, 48 H, 3 days (D), 7 D, 11 D, 15 D and 30 D). In addition, the toxicity of venom samples collected from mice at different stages was evaluated.</div><div>The volume of venom extracted by electrical stimulation was linearly related to body length. Body length and protein concentration were not correlated. When considering the multiple influences on production volume in <em>Buthus lienhardi</em>, the most important factor was body length, but volume was also positively associated with mesosome length and relative body mass. Male scorpions produced a greater volume of venom with a higher protein concentration than females.</div><div>For venom regeneration, the volume of venom extracted after depletion showed a significant increase over the days, reaching a complete recovery by day 11. In contrast, protein regeneration and toxicity were slower than that of volume, with a complete recovery observed by day 15.</div><div>This study should lead to the design of better venom extraction protocols for several studies such as treatment development, basic research and especially for drug development.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108254"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring ethnobotanical remedies: Medicinal plants for snakebite envenoming treatments in the Oued Righ region (Northern Algerian Sahara)","authors":"Aicha Mouane ,&nbsp;Alia Telli ,&nbsp;Aicha Tedjani ,&nbsp;Djouhain Achab ,&nbsp;Raba Djehiche ,&nbsp;Abdelouahab Gahtar ,&nbsp;Mounira Kadri ,&nbsp;Asma Abid ,&nbsp;Moufida Saoucen Alayat ,&nbsp;Nour El Houda Mekhadmi ,&nbsp;Abdallah Aouadi ,&nbsp;Maria Chikha ,&nbsp;Lotfi M'Hamdi ,&nbsp;Amar Djemoui ,&nbsp;Ayomide Victor Atoki ,&nbsp;Mohammed Messaoudi","doi":"10.1016/j.toxicon.2025.108259","DOIUrl":"10.1016/j.toxicon.2025.108259","url":null,"abstract":"<div><div>Snakebites present a significant health risk in the Sahara, where access to modern medical facilities is limited, leading local populations to rely on traditional remedies. The medicinal plants used by indigenous communities in the Oued Righ region of the Northern Algerian Sahara are vital for treating envenomation from snakebites. This study provides an ethnobotanical inventory of medicinal plants used by local communities in the Oued Righ region for snakebite treatment and evaluates their therapeutic potential. Ethnobotanical data were collected through structured surveys of 200 local residents, herbalists, and healers. Data were analyzed using ethnobotanical indices, including relative citation frequency (RFC), use value (UV), and family importance value (FIV). A total of 41 plant species from 23 families were identified, and their uses for snake envenomation were documented. The most frequently used plants were <em>Citrullus colocynthis</em> (14.95%) and <em>Nigella sativa</em> (10.74%), with Asteraceae being the most represented family. The remedies are predominantly prepared using aerial parts and seeds in various forms, such as poultices and decoctions. The ethnobotanical indices highlight the cultural importance and pharmacological potential of these plants. This study documents traditional knowledge on snakebite treatments, creating a foundational database for future pharmacological studies. The identified plant species hold significant potential for developing new antivenom therapies.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108259"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavior and oxidative stress evaluation of scorpion Tityus serrulatus (Lutz & Mello,1922) envenomation with genomic modulation and dopaminergic neutralization by antiscorpionic serum treatment","authors":"Rahisa Scussel ,&nbsp;Mírian Ívens Fagundes ,&nbsp;Gabriel Paulino Luiz ,&nbsp;Nathalia Coral Galvani ,&nbsp;Fernanda F. Gava ,&nbsp;Ellen De-Pieri ,&nbsp;Lariani Tamires Witt Tietbohl ,&nbsp;Taise Possamai-Della ,&nbsp;Jorge M. Aguiar-Geraldo ,&nbsp;Samira S. Valvassori ,&nbsp;Vanessa Moraes de Andrade ,&nbsp;Carlos Chávez-Olórtegui ,&nbsp;Ricardo Andrez Machado-de-Ávila","doi":"10.1016/j.toxicon.2025.108263","DOIUrl":"10.1016/j.toxicon.2025.108263","url":null,"abstract":"<div><div><em>Tityus serrulatus</em> accident promote vast symptomatology related to toxins of the venom, which leads to a massive release of neurotransmitters, notably dopamine, affecting behavior and neurochemistry. The recommended treatment for envenomation is the antiscorpionic serum (SAEsc) administration. Related to this complexity of the <em>Tityus serrulatus</em> envenomation, this study aimed to assess organism responses to the venom, its impact on behavior, oxidative stress, neurochemistry, and genetic impacts, as well as the efficacy of SAEsc, especially concerning dopamine levels and genetic interactions. Swiss mice were divided into groups and administered different venom concentrations intracerebroventricularly to assess behavioral impacts and brain oxidative stress. Oxidative stress was evaluated through reactive oxygen species (ROS) analysis and antioxidant assays, including dichloro-dihydro-fluorescein diacetate (DCF), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) measurements. Swiss mice were divided into four groups to evaluate genomic modulation, micronucleus enhancement, and dopamine levels. Additionally, SAEsc's neutralizing effect on dopamine was also investigated. Results showed that venom doses (100–300 ng/μL) increased lipid peroxidation in the brain, with SAEsc maintaining dopamine balance and neutralizing venom up to 24 h post-envenomation. After 24 h, cellular repair became less efficient, leading to mutagenic damage in both treated and untreated animals. The results highlight the importance of considering genomic and neurotransmitter function modulation in the treatment of <em>Tityus serrulatus</em> envenomation.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108263"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory effect of selective COX-2 inhibitor celecoxib on the neuropathological disorders and immunoinflammatory response induced by Kaliotoxin from Androctonus australis venom","authors":"Amina Ladjel-Mendil ,&nbsp;Nesrine Ahras-Sifi ,&nbsp;Hadjila Moussaoui ,&nbsp;Fatah Chérifi ,&nbsp;Fatima Laraba-Djebari","doi":"10.1016/j.toxicon.2025.108265","DOIUrl":"10.1016/j.toxicon.2025.108265","url":null,"abstract":"<div><div>The immune response is increasingly being linked to the pathogenic processes underlying neurological disorders including potassium channel malfunction. Few investigations, meanwhile, have shown how cyclooxygenase-2 (COX-2) is involved in the neuroimmunopathology linked to potassium channel failure. Thus, using an animal model of neuropathology caused by kaliotoxin, an exclusive blocker of voltage-gated potassium channels from the scorpion venom of <em>Androctonus australis hector</em>, we examined the immunomodulatory impact of celecoxib (selective inhibitor of COX-2). The neural and systemic pathogenic effects of KTX can be considerably reduced by celecoxib-mediated COX-2 inhibition, according to the results. It most certainly works via controlling the immunoinflammatory exposure by raising IL-10 levels; decreasing proinflammatory cytokine levels including mostly TNFα and IL-6, and balancing oxidative status. Along with that, by significantly promoting tissue healing, COX-2 inhibitor also enhances cellular metabolism. One potential treatment approach for immunoinflammatory exacerbations linked to neurodegenerative is the COX-2 inhibitor.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108265"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursolic acid enhances radiosensitivity in esophageal squamous cell carcinoma by modulating p53/SLC7A11/GPX4 pathway-mediated ferroptosis","authors":"Nuran Bedolla,&nbsp;Linyu Liu,&nbsp;Xueting Liu,&nbsp;Qiuxian Xie,&nbsp;Yanli Ren","doi":"10.1016/j.toxicon.2025.108233","DOIUrl":"10.1016/j.toxicon.2025.108233","url":null,"abstract":"<div><h3>Background</h3><div>Radiotherapy is essential for the management of esophageal squamous cell carcinoma (ESCC). However, ESCC cells are highly susceptible to developing resistance to radiotherapy, leading to poor prognosis. Ursolic acid (UA) is a herbal monomer, has multiple medicinal benefits like anti-tumor. The impact of UA on the sensitivity of ESCC cells to radiotherapy is currently unclear.</div></div><div><h3>Methods</h3><div>The impact of UA and ionizing radiation (IR) on the viability of TE-1 and KYSE30 cells was assessed by the MTT assay. EdU staining, flow cytometry, clone formation, Wound healing and Transwell assay detected the biological properties of ESCC cells. FerroOrange, DCFH-DA, and kits to detect the influences of UA and/or IR treatment on cellular ferroptosis. The levels of p53/solute carrier family 7a member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway proteins were detected by Western blot. Additionally, a subcutaneous graft tumor model was constructed in nude mice.</div></div><div><h3>Results</h3><div>10 μM UA reduced the viability and induced death of ESCC cells. UA enhanced the impacts of IR by suppressing cell proliferation, migration and invasion, inducing cell death, and causing cell cycle arrest. Ferroptosis inhibitor impaired the inhibitory impacts of UA and IR on the biological properties of ESCC cells. The combination of UA and IR led to ferroptosis through the modulation of the p53/SLC7A11/GPX4 pathway, and UA enhanced the responsiveness of ESCC cells to IR both <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>UA inhibits the malignant biological behavior of ESCC by modulating ferroptosis through the p53/SLC7A11/GPX4 pathway, and enhances the sensitivity of ESCC cells to IR.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"255 ","pages":"Article 108233"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}